faustmanw2008 updates 2

8/14/2019 FaustmanW2008 Updates 2

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W e are in the midst oour Phase I clinicaltrial evaluating the eects

o Bacillus Calmette-Gurin

(BCG) in type 1 diabetes. The

trial is being conducted here

at Massachusetts General

Hospital. Our lab recently

completed an exciting study

that confrms the mechanism

behind BCG, our potentialnew therapy.

The study, published in the

September 9, 2008 issue o the

Proceedings of the National

Academy of Sciences, was

conducted using human cells.

It showed that activating a

metabolic pathway that helps

regulate the immune system

specifcally eliminates the

deective T cells (a type o white

blood cell) that react against a

patients own tissues.

Previously, we had discovered

a technique that reversed type

1 diabetes in mice, which has

been the basis o our current

Phase I human clinical trial.

Our mouse studies showed

we could selectively kill the

deective T cells that were

destroying insulin-producing

islet cells o the pancreas.

Our latest study is the frst

demonstration that this

strategy also works in human

cells and supports the viability

o the clinical trial that is

currently underway.

In previous studies, our team

demonstrated that causing

diabetic mice to produce

elevated levels o tumor

necrosis actor (a substance

produced by the body that

helps to regulate the immune

system) leads to the death o

the deective T cells responsible

or the destruction o healthy

islet cells (cells in the pancreasthat produce insulin). Ater the

deective T cells were destroyed

and the immune system

became devoid o deective

cells, the mice were able to

regenerate healthy islet cells

that produced normal levels

o insulin. In other words,

the animals were cured o

their disease.

Updatesfrom the Faustman Laboratory at Massachusetts General Hospital

Fall/Winter 2008

MajorAdvancementin Potential New Therapyfor Type 1 Diabetes

Were launching a new web site

The Faustman Lab web site has undergone a

major redesign and includes expanded inormation.

Visit the site today at www.faustmanlab.org and

learn more about the trials and how you can

support them. You can also sign up or

e-mail updates.


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Our most recent studyused blood samples rommore than 1,000 people with

autoimmunity compared to

matched volunteers without

autoimmunity.

First, we ound in tissue culture

experiments the treatment with

tumor necrosis actor, or TNF,killed the deective T cells ound

in the blood o patients with type

1 diabetes and other autoimmune

diseases, but did not have any

eect on the healthy cells o the

control patients. This is a good

outcome because we want to

destroy only the deective cells,

and not the healthy ones. Then

we tested several substances,

called TNF agonists, that produce

an eect in the body similar to

that o TNF. We ound that one

o these substances was

also eective in destroying

the deective T cells in the

tissue culture o diabetic and

autoimmune patients, while

sparing healthy cells. Furtherexperiments with the blood

samples o diabetic patients

confrmed that our treatment

only leads to the death o the

deective T cells responsible

or producing an autoimmune

reaction (the attack o the islet

cells o the pancreas) in these

patients, and does not harm

healthy cells.

These fndings are important

because they provide urther

evidence and the frst in

human T cells in culture that

our approach in the current

human clinical trial does not

appear to harm healthy cells

and appears to kill in culture the

disease-causing cells.The current Phase I trial began

in January, 2008. In it, a generic

drug is being tested in patients

with type 1 diabetes to determine

whether the drug will cause the

death o the deective T cells that

destroy the pancreatic islet cells.

For more information, seeUpdate on the Clinical Trial.

New Way to Kill Defective CellsSpares Healthy Ones

Updates Fall/Winter 2008


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Our human clinical trialis testing whether usingBacillus Calmette-Gurin

(BCG), a generic drug that

temporarily elevates TNF levels

in the body, will reduce or

eliminate autoimmune T cells

in patients with type 1 diabetes.

The trials Phase I unding is

complete and the trial is in

progress under the direction

o Denise Faustman, MD,

PhD, and David Nathan, MD,

director o the MGH DiabetesCenter.

The trial, scheduled or

completion by January, 2010,

will gather inormation on drug

saety. Subsequent Phase II

trials will ocus on determining

the optimal dose and timing

o BCG administration to

achieve the desired eects in

type 1 diabetes. Phase I trials

are aimed at proving the drug

is sae.

While this trial is underway,

we need to begin planning or

our Phase II clinical trial, which

we hope to launch upon the

successul completion o thePhase I portion. The Phase II

trial will involve testing BCG

in greater numbers o patients

with type 1 diabetes using the

dose and timing we determine

rom the Phase I data. It will

also give us more inormation

on how eective this treatment

might be, providing the

inormation needed to launch

late-stage human clinical trials

(Phase III studies). We are

currently screening volunteers

or the Phase II trial.

A major part o the Phase II

planning involves raising the

unds needed to conduct thisnext stage o human research,

and we have set a und-raising

goal o $25 million.

Update on the Clinical Trial

In the MediaDenise Faustman, MD, PhD,on Talk of the Nations Science Friday

In September, Dr. Faustman had the privilege o joining radiohost Ira Flatow on National Public Radios Talk of the Nation. TheScience Friday segment discussed many aspects o diabetes, ourresearch and our current clinical trial. Here are some highlightsrom our conversation that address some aspects o the work beingdone at the Immunobiology Lab. For a ull transcript, please visitwww.faustmanlab.org.

Regarding our approach to eliminating thedisease-causing cells in type 1 diabetes:

FLATOW:And how do you go about killingthese bad white blood cells?

DR. FAUSTMAN: Oh, thats kind o the un parto this project, because were using a vaccinethats been out there or about 80 years, andthe vaccines called BCG. In the rest o the world,outside o the United States, its a mandatoryvaccine to prevent tuberculosis (TB).

In the U.S., its used or cancer. And the reasonwere interested in that vaccine is that it induces

something in your body called TNF, tumornecrosis actor. We think the way to kill onepopulation o these rogue T cells, whether yourea mouse or whether youre human, is with TNF.

FLATOW: And so youre trying that out inhumans now?

DR. FAUSTMAN: Yes were actually in humanclinical trials. Were not sure i the humans aregoing to be as happy as the mice;were very early in the process otesting it. But the Phase 1 trialsare ongoing here in Boston.

www.faustmanlab.


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In the spring o 2008, theBallet Foundation or theXXI Century dedicated its

Dance Festival to one o

the Foundations students,

Madeleine Howells. Madeleine

was diagnosed with diabetes

while in the second grade,

but never let the challengeget in the way o her passion

or dance. Now, at age 13,

Madeleine not only keeps up

with ballet, but also excels in

her class.

For the Foundations Dance

Festival 2008, a lyrical piece

was choreographed to eature

Madeleine. The piece, entitled

World, was arranged by the

companys prima ballerina,

Leia Hardimon, and set to

the music o artist Five or

Fighting.

The Ballet Foundation

generously collected

donations during the estival

to beneft Massachusetts

General Hospitals type 1diabetes research, and the

donations totaled more than

$1,400. We greatly admire

Madeleine or pursuing her

passion in spite o having this

challenging disease and we

would like to thank everyone

who was kind enough to make

a donation in support o our

research eorts.

Fund Raising:Creative Ways to Get Involved

Two Ways

You Can HelpPlease support theongoing research o ourlab with a tax-deductibledonation. Every git makesa dierence or patients today and tomorrow.

1. To make a secure onlinedonation, please visit

www.faustmanlab.organd click on Support.

2. You may make a gitby check (payable toMassachusetts GeneralHospital) and mail yourcheck to:

MGH Development OfceAttn: Jocelyn Hoey

165 Cambridge StreetSuite 600

Boston, MA 02114

On the memo line o yourcheck, please write: Type1 diabetes research orAutoimmune research.

Thank you or joining us inthe fght against diabetes.

Warmly,

Denise L. Faustman,MD, PhD

Updates Fall/Winter 2008

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